Development and early evaluation of clinical decision support for long QT syndrome population screening

Abstract

Aim: Long QT syndrome (LQTS) is an inherited condition that predisposes individuals to prolongation of the QT interval and increased risk for Torsade de Pointes. Pathogenic variants in three genes - KCNH2, KCNQ1 and SCN5A - are responsible for most cases of LQTS, and recent advances in genetic testing have improved knowledge of the disease, increased access to follow-up, and reduced adverse cardiovascular outcomes.

Methods: Based around our preemptive genetic screening platform which includes the three long QT genes listed above, we developed and implemented a clinical decision support (CDS) module that alerts prescribers whenever a QT-prolonging medication is ordered for patients with a genetic predisposition to LQTS.

Results: Of the 13,777 individuals screened, twenty-seven tested positive for a pathogenic or likely pathogenic variant of KCNH2, KCNQ1 or SCN5A. In a subsequent early evaluation of the CDS and clinical processes, the number of QT-prolonging medications in this cohort decreased by 20% and new QT-prolonging medications were avoided in approximately 1/3 of new prescription orders.

Conclusions: While long-term evaluation is needed, early data support the benefit of utilizing CDS in expanded roles, such as drug-gene-disease interactions where rare genetic variants intersect with everyday prescribing.

Keywords

Brugada syndrome / clinical decision support (CDS) / long QT syndrome (LQTS) / pharmacogenomics

References

[1] SchwartzPJ,CrottiL.Prevalence of the congenital long-QT syndrome.Circulation2009;120:1761-7 PMCID:PMC2784143

[2] NakanoY.Genetics of long-QT syndrome.J Hum Genet2016;61:51-5

[3] GiudicessiJR.Determinants of incomplete penetrance and variable expressivity in heritable cardiac arrhythmia syndromes.Transl Res2013;161:1-14 PMCID:PMC3624763

[4] WildeAAM.Clinical spectrum of SCN5A mutations: long QT syndrome, brugada syndrome, and cardiomyopathy.JACC Clin Electrophysiol2018;4:569-79

[5] SchwartzPJ,InsoliaR.Long-QT syndrome: from genetics to management.Circ Arrhythm Electrophysiol2012;5:868-77 PMCID:PMC3461497

[6] PrioriSG,SchwartzPJ.Low penetrance in the long-QT syndrome: clinical impact.Circulation1999;99:529-33

[7] SchwartzPJ.Idiopathic long QT syndrome: progress and questions.Am Heart J1985;109:399-411

[8] RohatgiRK,BosJM.Contemporary outcomes in patients with long QT syndrome.J Am Coll Cardiol2017;70:453-62

[9] PrioriSG,HorieM.HRS/EHRA/APHRS expert consensus statement on the diagnosis and management of patients with inherited primary arrhythmia syndromes: document endorsed by HRS, EHRA, and APHRS in May 2013 and by ACCF, AHA, PACES, and AEPC in June 2013.Heart Rhythm2013;10:1932-63

[10] Al-KhatibSM,AckermanMJ.2017 AHA/ACC/HRS guideline for management of patients with ventricular arrhythmias and the prevention of sudden cardiac death: a report of the American college of cardiology/American heart association task force on clinical practice guidelines and the heart rhythm society.J Am Coll Cardiol2018;72:e91-e220

[11] SchwartzPJ,CerroneM.Left cardiac sympathetic denervation in the management of high-risk patients affected by the long-QT syndrome.Circulation2004;109:1826-33

[12] SchwartzPJ.Cardiac sympathetic denervation in the prevention of genetically mediated life-threatening ventricular arrhythmias.Eur Heart J2022;43:2096-102

[13] DusiV,DeFerrari GM.Left cardiac sympathetic denervation for long QT Syndrome: 50 Years’ experience provides guidance for management.JACC Clin Electrophysiol2022;8:281-94

[14] JohnsonJN.Competitive sports participation in athletes with congenital long QT syndrome.JAMA2012;308:764-5

[15] ChristensenKD,ZawatskyCLB.Precision population medicine in primary care: the sanford chip experience.Front Genet2021;12:626845 PMCID:PMC7994529

[16] NatashaPetry,AifaouiA.Implementation of wide-scale pharmacogenetic testing in primary care.Pharmacogenomics2019;20:903-13

[17] SoritaA,MorlanBW,AckermanMJ.Impact of clinical decision support preventing the use of QT-prolonging medications for patients at risk for torsade de pointes.J Am Med Inform Assoc2015;22:e21-7 PMCID:PMC5901125

[18] TrinkleyKE,MartinezDD,HaleG.Assessing prescriber behavior with a clinical decision support tool to prevent drug-induced long QT syndrome.Appl Clin Inform2021;12:190-7 PMCID:PMC7946597

[19] HymelN.Evidence-based antiemetic decision tool for management of postoperative nausea and vomiting in patients at high risk of QT prolongation and patients receiving neurotransmitter-modulating medications.AANA J2020;88:312-8

[20] SchwartzPJ.Predicting the unpredictable: drug-induced QT prolongation and torsades de pointes.J Am Coll Cardiol2016;67:1639-50

[21] GrissingerM.Selected medication safety risks that can easily fall off the radar screen.P T2018;43:521-67

[22] MillerDT,ChungWK.ACMG SF v3.0 list for reporting of secondary findings in clinical exome and genome sequencing: a policy statement of the American College of Medical Genetics and Genomics (ACMG).Genet Med2021;23:1381-90

[23] BayeJF,JacobsonSL.Malignant hyperthermia susceptibility: utilization of genetic results in an electronic medical record to increase safety.Pharmacogenomics2020;21:1207-15